title: Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion.
abstract: We tested the hypothesis that increasing blood amino acid (AA) availability would counter the physical inactivity-induced reduction in muscle protein synthesis. We determined how 14 days of unilateral knee immobilization affected quadriceps myofibrillar protein synthesis (MPS) in young healthy subjects (10 men, 2 women, 21 +/- 1 years; 80.2 +/- 4.0 kg, mean +/- S.E.M.) in the post-absorptive state and after infusing AA (10% Primene) at low or high doses (43 and 261 mg kg(-1) h(-1)). Muscle cross-sectional area (MRI) and peak isometric torque declined in the immobilized leg (-5.0 +/- 1.2% and -25 +/- 3%, respectively, both P < 0.005), but were unchanged (all P > 0.6) in the non-immobilized leg. Immobilization induced a 27% decline in the rate of post-absorptive MPS (immobilized, 0.027 +/- 0.003: non-immobilized, 0.037 +/- 0.003% h(-1); P < 0.001). Regardless of dose, AA infusion stimulated a greater rise in MPS in the non-immobilized legs; at 4 h MPS was greater by +54 +/- 12% with low dose and +68 +/- 17% with high dose AA infusion (both P < 0.001). There was some evidence of delayed responsiveness of phosphorylation of Akt to high doses of AA and p70S6k at both doses but no marked differences in that of mTOR, GSK3beta or eEF2. Phosphorylation of focal adhesion kinase (Tyr(576/577)) was reduced (P < 0.05) with immobilization. We observed no change in polyubiquitinated protein content after immobilization. We confirm that 14 days of immobilization reduces MPS in the post-absorptive state and this diminution is reduced but not abolished by increased provision of AA, even at high rates. The immobilization-induced decline in post-absorptive MPS with the 'anabolic resistance' to amino acids can account for much of immobilization-induced muscle atrophy.
authors.affiliation: Department of Kinesiology - Exercise Metabolism Research Group, McMaster University, 1280 Main St West, Hamilton, ON L8S 4K1, Canada.
authors.forename: Elisa I
authors.initials: EI
authors.lastname: Glover
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Phillips
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Oates
authors.forename: Jason E
authors.initials: JE
authors.lastname: Tang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.forename: Anna
authors.initials: A
authors.lastname: Selby
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rennie
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000601:Amino Acids, Essential / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054736:Elongation Factor 2 Kinase / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007103:Immobilization / Q000379:methods; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D009210:Myofibrils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D054875:Ubiquitination / Q000187:drug effects; D055815:Young Adult
chemical_list: D000596:Amino Acids; D000601:Amino Acids, Essential; D007328:Insulin; D009124:Muscle Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D054736:Elongation Factor 2 Kinase; D038362:Glycogen Synthase Kinase 3